Radiation therapy and bromodeoxyuridine chemotherapy followed by procarbazine, lomustine, and vincristine for the treatment of anaplastic gliomas

Abstract

Purpose : To conduct a Phase II study to evaluate the long-term efficacy and safety of radiotherapy combined with intravenous bromodeoxyuridine for patients with anaplastic glioma tumors. Methods and Materials : Between 1983 and 1987, study patients received 1.7–1.8 Gy radiation once a day, Monday through Friday, to a toatl dose of 60 Gy. On the Thursday prior to beginning radiotherapy and for the next 5 weeks (6 weeks total), patients received a continuous 96 h intravenous infusion of bromodeoxyuridine at 0.8 g/m 2/24 h; following radiotherapy, patients received procarbazine, lomustine (CCNU), and vincristine (PCV) for 1 year or until tumor progressed. Results : One-hundred thirty eight patients (median age, 43 years) were evaluated for analysis. Estimated 4-year survival for the anaplastic astrocytoma (AA) stratum ( n = 116) is 46%. For the astrocytoma (ASTRO) stratum ( n = 22), the 6-year survival is estimated at 79%. Estimated 4-year progression-free survival for AAs is 42%, and for ASTROs, 68%. Whole brain irradiation was used in 23% and limited-field irradiation in 77%; patients receiving limited-field irradiation had a better survival rate ( p = 0.07). Total tumor resection was performed in 15%, partial resection in 53%, and biopsy only in 32%. For the 81 patients with tumor recurrence, 34 (42%) are known to have received additional treatment(s). For AA, fits of the Cox proportional hazards regression model showed that covariates individually predictive of survival were younger age ( p < 0.001), Karnofsky performance score ( p = 0.04), and extent of surgery ( p = 0.04); limited-field irradiation was not significant ( p = 0.10). Major toxicities were rash during Weeks 1 through 6 requiring dose modification in 14%, Garde ≥III leukopenia in 18%, and Grad ≥III thrombocytopeni in 9%. Conclusion : The study suggests that the bromodeoxyuridine-radiotherapy-PCV, compared with other published therapies, can improve progression-free survival, and aggressive treatment of ASTRO patients can lead to substantial increases in survival compared to published survival data.